Medical endoprostheses or implants for a wide range of applications are known in a large variety from the prior art. Implants in the meaning of the present invention are to be understood as endovascular prostheses or other endoprostheses, for example stents, in particular wire mesh stents, fastener elements for bones, for example screws, plates or nails, medullary nails, spiral bundle nails, Kirschner-nails, wires for septal occluders, surgical sutures, intestinal staples, vascular clips, prostheses in the region of the hard and soft tissue, and anchor elements for electrodes, in particular of pacemakers or defibrillators.
Today, particularly frequently used as implants are stents which serve for the treatment of stenoses (vasoconstrictions). Stents have a body, if applicable, in the form of an open-worked tubular or hollow-cylindrically grid which is open at both longitudinal ends. The tubular grid of such an endoprosthesis is inserted into the vessel to be treated and serves for supporting the vessel. Stents are established in particular for the treatment of vascular diseases. By using stents or other implants, constricted areas in the vessels can be expanded, thereby resulting in a lumen gain. By using stents or other implants, an optimal vessel cross-section, which is primarily necessary for the success of the therapy, can be achieved; however, the permanent presence of such a foreign body initiates a cascade of microbiological processes which can result in a gradual constriction of the stent, and in the worst case in a vascular occlusion. An approach for the solution of this problem is to produce the stent or other implants from a biodegradable material.
Biodegradation is to be understood as hydrolytic, enzymatic and other metabolic-related degradation processes in a living organism which are mainly caused by body liquid which gets in contact with the biodegradable material of the implant and which result in a gradual degradation of the structures of the implant containing the biodegradable material. Through this process, the implant loses its mechanical integrity at a certain point in time. As a synonym for the term biodegradation, the term biocorrosion is frequently used. The terms bioresorption comprises the subsequent resorption of the degradation products by the living organism.
Suitable materials for the body of biodegradable implants can contain, for example, polymers or metals. The body can consist of a plurality of said materials. A common feature of said materials is their biodegradability. Examples for suitable polymeric compounds are polymers from the group cellulose, collagen, albumin, casein, polysaccharides (PSAC), polyactide (PLA), poly-L-lactide (PLLA), polyglycol (PGA), poly-D,L-lactide-co-glycolide, (PDLLA-PGA), polyhydroxybutyrate (PHB), polyhydroxyvaleric acid (PHV), polyalkyle carbonate, polyorthoester, polyethylene terephthalate (PET), polymalonic acid (PML), polyanhydrides, polyphosphazenes, polyamino acids and their co-polymers, and hyalaronic acid The polymers can be available depending on the desired properties in pure form, in derivatized form, in the form of blends or as co-polymers. Metallic biodegradable materials are primarily based on alloys of magnesium and iron. The present invention relates preferably to implants, the body of which consists primarily of a biodegradable material with iron as the main constituent, in particular of an iron-based alloy (hereinafter in short: iron alloy).
When implementing biodegradable implants, it is intended to control the degradability according to the intended therapy or the application of the respective implant (coronary, intracranial, renal, etc.). For many therapeutic applications it is, for example, an important target corridor that the implant loses its integrity within a time period of four weeks to six months. Here, integrity, i.e., mechanical integrity, is to be understood as the property that the implant has barely any mechanical shortcomings with respect to the non-degradable implant. This means that the implant is mechanically stable such that, for example, the collapse pressure has dropped only insignificantly, i.e., not below 80% of the nominal value. Thus, with existing integrity, the implants still meet its main function which is to ensure the penetrability of the vessel. Alternatively, integrity can be defined in that the implant is mechanically stable such that it is barely subject of any geometrical changes in its loaded state in the vessel, for example, does not collapse significantly, i.e., shows under load at least 80% of the dilatation diameter or, in case of a stent, has barely any partially fractured supporting webs.
Implants with an iron alloy, in particular ferrous stents, are producible in a particularly inexpensive and simple manner. However, for example for the treatment of stenoses, these implants lose their mechanical integrity or supporting effect only after a relatively long period of time, i.e. only after a retention period in the treated organism of approximately two years. This means that the collapse pressure for ferrous implants decreases too slow over time for this application.
A long retention period of implants can cause complications during the further treatment of the patient, namely, for example, if the dissolving implant, due to its ferromagnetic properties, does not allow or considerably affects the examination of the patient in the magnetic resonance scanner. Further, a presence of the stent in the vascular wall exceeding the necessary retention time can result in mechanical irritations therein which, in turn, can result in re-constriction of the vessel to be treated. Moreover, in case of orthopedic implants (e.g. bone plates), the formation of new bone substance can result in mechanical stress between the implant which degrades too slow and the new bone substance. This generates, in particular in children and adolescents, bone deformations or defects. For such applications it is thus desirable if the range of applications of implants, the body of which comprises at least primarily a material with the main constituent iron, can be broadened by faster degradation.
In the prior art, different mechanisms for controlling degradation of implants have already been described. They are based, for example, on inorganic or organic protection layers or their combinations which resist the human corrosive environment and the corrosion processes taking place therein. Previously known solutions are characterized in that barrier layer effects are achieved which are based on a spatial and preferably defect-free separation of the corrosion medium from the metallic medium. Said effects result in that the degradation time is extended. Thus, the degradation protection is ensured through differently composed protection layers and by defined geometrical distances (diffusion barriers) between the corrosion medium and the basic material. Further solutions in the field of the controlled degradation cause the effects of predetermined breaking points by physically changing (e.g. local cross-section changes) the stent surface (e.g. multi-layers with locally differing compositions). Other previously described methods concentrate on initiating the corrosion processes by introducing defects close to the surface and to achieve a corrosion increase in the further course by means of the increasing real surface forming thereby. Another possibility is to combine these effects from the beginning with the increase of the original surface roughness values and thus to increase the binding tendency, for example of chlorides, in such a manner that they result, in connection with increased environment humidity or in vivo, in an accelerated corrosion. However, with the above mentioned solutions it is in most cases not possible to bring the dissolution initiated by the degradation process and the resulting web breakages in the desired time window. The consequence is a degradation that starts too early or too late, or an excessive variability of the degradation of the implant.
From the printed publications EP 0 923 389 B1 or WO 99/03515 A2, or WO 2007/12430 A1, implants are known which are degradable in vivo by corrosion. The material of the known implants contains iron as main constituent and carbon in a certain predetermined concentration. The disadvantage of these alloys is that, with increasing carbon content, the binary system from carbon and iron loses significant ductility without the corrosion resistance decreasing to the same extent.
From the printed publication DE 10 2008 002 601 A1, an implant having a base body is known which consists completely or in parts of a biocorrodible iron alloy. Here, the biocoordible iron alloy has the formula Fe—P, wherein a portion of P of the alloy is 0.01 to 5% by weight and Fe as well as production-related impurities represents the remaining balance to 100% by weight of the alloy. However, the disadvantage of the known alloy is that with increased P-content, the ductility of the material decreases and it is thus more difficult to process. However, the addition of P results in an increase of the hardness of the material. Mn as an alloying constituent, which is also mentioned in the document, serves as additive for the separation of fine-phased, Pd-containing intermetallic compounds which can only be generated by alloying noble metals and/or heavy metals. However, the use of noble metals or heavy metals is often problematic and increases the cost.
In the printed publication DE 10 2004 036 954 A1, an implantable body for the intersomatic fusion (spinal fusion) is produced which is made of a bioresorbable metallic material. The metallic material comprises as main constituent alkaline metals, alkaline earth metals, iron, zinc or aluminum. As minor constituents, manganese, cobalt, nickel, chromium, copper, cadmium, lead, tin, thorium, zirconium, silver, gold, palladium, platinum, rhenium, silicon, calcium, lithium, aluminum, zinc, carbon, sulfur, magnesium and/or iron can be used. The advantage of such a material is that the material has particularly advantageous mechanical properties, in particular with respect to elasticity, deformability and stability at low mass. However, the degradation of the material is not within the desired time window.
Further examples of implants which consist of a biodegradable iron alloy are disclosed in the printed publications DE 197 31 021 A1 and WO 2007/082147 A2. In the mentioned printed publications, iron alloys with nickel and chromium are described which, in particular if they are not electropolished, release nickel ions. Nickel ions cause negative inflammatory effects not only in nickel-allergic persons. Chromium ions too, if present in a mean concentration range up to 12% by weight, can be released individually or together with other heavy metals and can potentially cause negative cell reactions. In case electropolishing is carried out, the release of nickel ions is reduced, but the degradation time is extended in a disadvantageous manner due to the formation of passivation layers.